The contractor will evaluate the clinical, virologic and toxicologic effects of putative antiviral agents directed at the management of herpes simplex viruses (HSV) types 1 and 2, cytomegalovirus (CMV) and varicella zoster virus (VZV). They will utilize guinea pig model systems because these models exhibit pathophysiological features analogous to the corresponding infection in humans. Human strains of HSV and VZV will be utilized; however, they will employ guinea pig CMV since it is not possible to infect guinea pigs with human CMV. The contractor will first test the candidate compounds for in vitro activity in fetal guinea pig cells against the test virus strain intended for animal inoculation. They will explore for potential drug toxicity in the animal model system. They will then evaluate the experimental therapeutic agents as potential drugs for the treatment of varicella, primary and recurrent genital herpes, neonatal herpes, and cytomegalovirus infections exploring for drug efficacy, toxicity and changes in the pathophysiology of infection. In addition to these studies, they will further refine their recently described guinea pig model of neonatal HSV infection to determine the usefulness of this experimental system to predict neurologic outcome of infection and treatment.